Autoimmune diseases affect approximately 5-8% of the population in the United States. Fairweather, D., Autoimmune Disease: Mechanisms, Encyclopedia of Life Sciences (2007). Many autoimmune diseases affect young persons and may persist over the lifetime of the individual, leading to a disproportionate burden on public health resources and an annual estimated cost of over 100 billion dollars in the United States.
Autoreactive T cells are key players in autoimmune diseases, acting as both helper and effector cells. Dornmair, K., et al., T-Cell-Mediated Autoimmunity, Am. J. Pathol. 163(4):1215-26 (2003). Studies have shown that the transfer of autoreactive T cells is sufficient to induce autoimmune disease in animal models.
T cells have been shown to mediate a variety of autoimmune diseases, including type 1 diabetes, multiple sclerosis, systemic lupus, psoriasis, and rheumatoid arthritis, and probably play a role, as a part of a coordinated immune response, in many other autoimmune diseases. T regulatory cells suppress immune responses of other cells, including autoreactive T cells, although the molecular mechanisms by which regulatory T cells exert suppressor activity have not been completely characterized. T-cells contribute to most autoimmune diseases, many of which are severely debilitating and may lead to patient death. For example, type 1 diabetes (T1D) remains a major cause of long-term morbidity and mortality in over one percent of population worldwide. Although insulin treatment and islet transplantation are currently the most effective therapeutic regimens, these approaches suffer from limitations and are not always effective to treat the disease. To date, although autoreactive T cells have been proven to mediate T1D, no effective immune-based therapy has reversed T1D. Thus, immune-based therapies modulating autoreactive T cells are desperately needed in T1D. The same holds true for other diseases, such as multiple sclerosis. The need persists for methods and compositions that treat or prevent T-cell-mediated autoimmune disorders.